Excessive bleeding or hemorrhaging has always been a significant issue with many medical or surgical procedures. Because of this, the medical industry has continuously sought new and improved products to inhibit bleeding in a patient, and methods of establishing hemostasis. In general, these hemostatic products and processes assist in the rapid initiation of a hemostatic plug formed through platelet activation, aggregation, adhesion and gross clot formation at a tissue target site.
A wide variety of hemostatic products are made from different base materials, such as collagen, gelatin, oxidized regenerated cellulose, fibers, gauze sponges and fibrin. These products are used in a wide variety of medical and surgical procedures. For example, microfibrillar collagen is used extensively for wide-area parenchyma bleeding and for laparoscopic procedures. Hemostatic sponges are used in surgical as well as dermatological applications where adherence to the wound site and ease of removal are important considerations.
A number of hemostatic collagen-containing devices have previously been described. For example, U.S. Pat. Nos. 5,428,024; 5,352,715; and 5,204,382 generally relate to fibrillar and insoluble collagens that have been mechanically disrupted to alter their natural physical properties. Injectable collagen compositions are described in U.S. Pat. Nos. 4,803,075 and 5,516,532. International application WO 96/39159 describes a collagen-based delivery matrix made of dry particles in the size range from 5 μm to 850 μm, where the particles are suspended in water and have a particular surface charge density. A bioactive agent is then incorporated in the matrix prior to administration to a patient. U.S. Pat. No. 5,196,185 describes a collagen preparation having a particle size from 1 μm to 50 μm useful as an aerosol spray to form a wound dressing. U.S. Pat. No. 7,320,962 describes a hemostatic composition having a population of crosslinked polymer (e.g. gelatin or collagen) integrated into a non-crosslinked polymer (e.g. gelatin or collagen) population, such that the non-crosslinked collagen dissolves at the wound site, releasing the crosslinked collagen to form a hemostatic hydrogel. U.S. Pat. Nos. 6,063,061; 6,066,325 and 6,706,690 also describe hemostatic compositions that include soluble and/or non-fibrillar collagen, with plasticizers and hemostatic agents, such as thrombin, integrated within the composition.
Collagen pads have also been used to improve wound healing or to stop bleeding, via platelet aggregation and activation, the formation of thrombin on the surface of activated platelets, and the formation of a hemostatic fibrin clot by the catalytic action of thrombin on fibrinogen. Hemostatic agents are typically added to the collagen pads. For example, in U.S. Pat. No. 4,600,574 a collagen based tissue adhesive combined with fibrinogen and factor XIII is described. The fibrinogen and factor XIII are combined with the collagen by impregnating the flat collagen material with a solution comprising fibrinogen and factor XIII, and lyophilizing the material. U.S. Pat. No. 5,614,587 describes bioadhesive compositions comprising crosslinked collagen using a synthetic hydrophilic polymer.
However, because no single device or process can meet the dynamic applications of the medical industry, there continues to be a need to provide alternative systems and methods for achieving hemostasis, particularly compositions that do not require the use of additional hemostatic agents, such as thrombin. Thus, there continues to be a need for flowable hemostatic compositions that can easily be delivered to tissue and establish hemostasis without delaying or inhibiting tissue repair. There is also a need for hemostatic compositions that promote wound healing; and hemostatic compositions that readily adhere to the tissue but not to surgical materials, such as gauze. The present invention satisfies this need.